Inhibitory Effects Of Triterpenoid Betulin On Inflammatory Mediators Inducible Nitric Oxide Synthase, Cyclooxygenase-2, Tumor Necrosis Factor-Alpha, Interleukin-6, And Proliferating Cell Nuclear Antigen In 1,2-Dimethylhydrazine-Induced Rat Colon Carcinogenesis

Background: Colon carcinogenesis is the third most commonly occurring malignant neoplasm and the second most common cause of cancer-related deaths globally. Betulin (BE) is a pentacyclic lupane-type triterpenoid naturally dispersed in many plants. It is also recognized as betuline, betulinol, or betulinic alcohol. Objectives: In this study, we explored the anticancer, antiproliferative, and anti-inflammatory effects of BE on 1,2-dimethylhydrazine (DMH)-treated rat model of colon cancer. Materials and Methods: Colon cancer was induced by a subcutaneous injection of DMH (20 mg/kg bwt) once a week for the initial 4 weeks of the experiment. We analyzed body weight, tumor incidence, tumor volume, total number of tumors, thiobarbituric acid reactive substances (TBARS), and levels of antioxidants (glutathione peroxidase, glutathione, catalase, and superoxide dismutase), bacterial enzymes (beta-glucuronidase and mucinase), Phase I (cytochrome P450 and cytochrome b5) and Phase II (GST and Glutathione reductase (GR)) detoxification enzymes, and inflammatory (cyclooxygenase-2, interleukin-1 beta [IL-1 beta], inducible nitric oxide synthase, tumor necrosis factor-alpha, and IL-6) and cell proliferative (cyclin D1 and proliferating cell nuclear antigen) markers. We also assessed the histopathological alterations found in experimental and control rats. Results: We observed decreased body weight and levels of antioxidants and Phase II enzymes; augmented tumor incidence, tumor volume, total number of tumors, Phase I enzymes, TBARS, and levels of bacterial enzymes; and irregular histopathological changes in DMH-treated rats. Moreover, the Western blotting analysis of colon tissues revealed upregulation of inflammatory and cell proliferative markers in DMH-treated rats. Oral supplementation of 20 mg/kg bwt BE led to inhibition of tumor formation and inflammation, regulation of cell proliferation, and restoration of biochemical parameters. Our findings were supported by histopathological analysis. Conclusion: Our results suggested that BE exhibited anticancer, anti-inflammatory, and antiproliferative effects against DMH-induced colon cancer in rats.